Hypertrophy is a biologic response which usually occurs when an organ's work is chronically increased. A common finding in cardiac pathology is that the hearts of patients with diffuse coronary atherosclerosis often demonstrate the same characteristics as those with long-standing aortic stenosis, i.e. fibrotic, non-compliant, hypertrophied ventricles. Both conditions create a prolonged alteration in the normal balance between work requirements and oxygen or substrate availability. This alteration may trigger a series of intracellular biochemical reactions that generate a molecular stimulus for protein synthesis and, hence, hypertrophy. We have demonstrated, in preliminary work, that a heart provoked to hypertrophy by aortic banding synthesizes or releases molecules that can be extracted and used to induce hypertrophy (as measured by increased RNA synthesis) in a heart not otherwise subjected to stress and that a kidney provoked to hypertrophy by contralateral nephrectomy, also, synthesizes or releases molecules which can be extracted and used to induce cardiac hypertrophy. We propose to determine the generality of these observations by testing the ability of other organs, when stressed, to generate extractable substances which can be used to stimulate RNA synthesis in organs under non-stressed conditions. The studies will be carried out by measuring RNA translational activity in isolated organ preparations maintained in an essentially normal circulatory and physiological environment. We also propose to fractionate the extract and attempt to isolate and identify the active molecules which initiate RNA synthesis. Incubation of tissue slices in media containing fractionation products will provide the basis for the assay system. These studies are designed to increase our understanding of the control mechanisms for cell growth and division and to provide a rational basis for developing techniques to treat diseases, which, as one of their effects, induce alterations of cell size and number.